The Chemoenzymatic Total Synthesis of Phellodonic Acid, a Biologically Active and Highly Functionalized Hirsutane Derivative Isolated from the Tasmanian Fungus Phellodon melaleucus

Tristan A. Reekie; Kerrie A. B. Austin; Martin G. Banwell; Anthony C. Willis

doi:10.1071/CH07403

RESEARCH ARTICLE

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The Chemoenzymatic Total Synthesis of Phellodonic Acid, a Biologically Active and Highly Functionalized Hirsutane Derivative Isolated from the Tasmanian Fungus Phellodon melaleucus

Tristan A. Reekie ^A , Kerrie A. B. Austin ^A , Martin G. Banwell ^A ^B and Anthony C. Willis ^A

+ Author Affiliations

- Author Affiliations

^A Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia.

^B Corresponding author. Email: mgb@rsc.anu.edu.au

Australian Journal of Chemistry 61(2) 94-106 https://doi.org/10.1071/CH07403
Submitted: 21 November 2007 Accepted: 3 January 2008 Published: 11 February 2008

Abstract

A total synthesis of the title natural product, 1, has been achieved using the cis-1,2-dihydrocatechol 7 as starting material. Compound 7 is readily obtained in large quantity and in an enantiomerically pure form through the whole-cell biotransformation of toluene using the genetically engineered microorganism E. coli JM109 (pDTG601) that overexpresses the enzyme toluene dioxygenase (TDO). Three key chemical steps were employed in the synthesis, the first of which was the microwave-promoted Diels–Alder cycloaddition reaction between diene 8 and cyclopent-1-en-2-one to give adduct 9. The second key step was the photochemically promoted oxa-di-π-methane rearrangement of the bicyclo[2.2.2]octenone derivative 15 of 9 to give the epimers 16 and 17, and the third key step was the reductive cleavage of the last pair of compounds so as to afford the linear triquinane 19. Elaboration of compound 19 to target 1 followed established procedures. Single-crystal X-ray analyses were carried out on compounds 11 and 19.

Acknowledgements

We thank the Institute of Advanced Studies and the Australian Research Council for generous financial support. Professor Wolfgang Steglich (LMU, Munich) is warmly acknowledged for providing copies of the original ¹H and ¹³C NMR spectra of the naturally-derived phellodonic acid (1).

References

^* Compound 7 can be obtained from Questor, Queen’s University of Belfast, Northern Ireland (see: http://questor.qub.ac.uk/newsite/contact.htm).

The Chemoenzymatic Total Synthesis of Phellodonic Acid, a Biologically Active and Highly Functionalized Hirsutane Derivative Isolated from the Tasmanian Fungus Phellodon melaleucus

Abstract

Acknowledgements

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